U.S. patent application number 10/135978 was filed with the patent office on 2003-10-30 for coated conditioners for use in foods and pharmaceuticals.
Invention is credited to Cornelius, John Mark, Freeman, Gary M., Neades, June M., Tarquini, Michael E..
Application Number | 20030203019 10/135978 |
Document ID | / |
Family ID | 34797955 |
Filed Date | 2003-10-30 |
United States Patent
Application |
20030203019 |
Kind Code |
A1 |
Cornelius, John Mark ; et
al. |
October 30, 2003 |
Coated conditioners for use in foods and pharmaceuticals
Abstract
An edible composition comprising a coated conditioner that
contains a hydrophobization agent and inorganic particles is
provided. When incorporated into an edible composition (such as a
powdered pharmaceutical or food product), the coated conditioners
inhibit caking and promote the free flow of powder. Suitable
hydrophobization agents include food-grade fatty acids, food-grade
oils, food-grade waxes, and food-grade gums, while suitable
inorganic particles are selected from the group consisting of
silica, silicates, calcium carbonates, phosphates, and clays. The
coated conditioner is particularly suitable for use in
pharmaceutical preparations, such as acetaminophen.
Inventors: |
Cornelius, John Mark;
(Forest Hill, MD) ; Tarquini, Michael E.; (Havre
de Grace, MD) ; Neades, June M.; (Havre de Grace,
MD) ; Freeman, Gary M.; (Macon, GA) |
Correspondence
Address: |
David Mitchell Goodrich, Esq.
J. M. Huber Corporation
333 Thornall Street
Edison
NJ
08837-2220
US
|
Family ID: |
34797955 |
Appl. No.: |
10/135978 |
Filed: |
April 30, 2002 |
Current U.S.
Class: |
424/465 ;
514/629 |
Current CPC
Class: |
A61K 47/02 20130101;
A23L 19/01 20160801; A23V 2002/00 20130101; A23P 10/35 20160801;
A61K 47/12 20130101; A23L 27/14 20160801; A61K 31/16 20130101; A23V
2002/00 20130101; A61K 9/143 20130101; A23V 2250/1628 20130101;
A23V 2200/224 20130101; A23V 2200/208 20130101; A23V 2250/212
20130101; A23V 2250/1628 20130101; A23V 2250/1886 20130101; A23V
2002/00 20130101; A23V 2250/1886 20130101; A23P 10/43 20160801;
A61K 47/14 20130101 |
Class at
Publication: |
424/465 ;
514/629 |
International
Class: |
A61K 009/20; A61K
031/16 |
Claims
We claim:
1. An edible composition comprising a coated conditioner, the
conditioner containing a hydrophobization agent and inorganic
particles.
2. The edible composition according to claim 1, wherein the
hydrophobization agent is selected from the group consisting of
food-grade fatty acids, food-grade oils, food-grade waxes, and
food-grade gums.
3. The edible composition according to claim 1, wherein the
hydrophobization agent is a stearic compound.
4. The edible composition according to claim 1, wherein the
hydrophobization agent is magnesium stearate.
5. The edible composition according to claim 1, wherein the
hydrophobization agent is selected from the group consisting of
stearic acid salts and stearic acid esters.
6. The edible composition according to claim 1, wherein the
inorganic particles are selected from the group consisting of
silica, silicates, calcium carbonates, phosphates, and clays.
7. The edible composition according to claim 1, wherein the
conditioner comprises about 1 wt % to about 10 wt %, based on the
total weight of the conditioner, of the hydrophobization agent.
8. The edible composition according to claim 1, wherein the
hydrophobization agent is selected from the group consisting of
glyceryl-monostearate and glyceryl tristearate.
9. The edible composition according to claim 1, wherein the
composition is a powdered food product.
10. The edible composition of claim 1, wherein the edible
composition is a pharmaceutical preparation, and further comprises
a pharmaceutically active ingredient.
11. The pharmaceutical preparation of claim 10, wherein the
preparation is in the form of a powder.
12. The pharmaceutical preparation of claim 10, wherein the
preparation is in the form of a tablet.
13. The pharmaceutical preparation of claim 10, wherein the
pharmaceutically active ingredient is acetaminophen.
14. The pharmaceutical preparation of claim 10, wherein the
pharmaceutically active ingredient is selected from the group
consisting of nourishing and health-promoting agents,
antipyretic-analgesic-antiinfl- ammatory agents, antipsychotic
drugs, antianxiety drugs, antidepressants, hypnotic-sedatives,
spasmolytics, central nervous system affecting drugs, cerebral
metabolism ameliolators, antiepileptics, sympathomimetic agents,
gastrointestinal function conditioning agents, antacids, antiulcer
agents, antitussive-expectorants, antiemetics, respiratory
stimulants, bronchodilators, antiallergic agents, dental buccal
drugs, antihistamines, cardiotonics, antiarrhythmic agents,
diuretics, hypotensive agents, vasoconstrictors, coronary
vasodilators, peripheral vasodilators, antihyperlipidemic agents,
cholagogues, antibiotics, chemotherapeutic agents, antidiabetic
agents, drugs for osteoporosis, skeletal muscle relaxants,
antidinics, hormones, alkaloid narcotics, sulfa drugs,
antipodagrics, anticoagulants, anti-malignant tumor agents, and
treatment agents for Alzheimer's disease.
15. The edible composition of claim 3, wherein the inorganic
particles are coated with the stearic compound.
16. The edible composition according to claim 1, wherein the
hydrophobization agent is selected from alkaline earth
stearates.
17. The edible composition according to claim 1, wherein the
hydrophobization agent is a food-grade mineral oil.
18. The edible composition according to claim 1, wherein the
conditioner comprises about 1 wt % to about 20 wt %, based on the
total weight of the conditioner, of food-grade mineral oil.
19. The pharmaceutical preparation of claim 1, wherein the
hydrophobization agent is present in a concentration of about 1 wt
% to about 20 wt %, based on the total weight of the
conditioner.
20. A pharmaceutical preparation comprising a pharmaceutically
active ingredient and a coated conditioner, the conditioner
containing inorganic particles and a hydrophobization agent.
21. The pharmaceutical preparation of claim 20, wherein the
pharmaceutically active ingredient is acetaminophen.
22. The pharmaceutical preparation of claim 20, wherein the
pharmaceutical preparation is in the form of a tablet.
23. The pharmaceutical preparation of claim 20, wherein the
hydrophobization agent is present in a concentration of about 1 wt
% to about 20 wt %, based on the total weight of the
conditioner.
24. The pharmaceutical preparation of claim 20, wherein the
hydrophobization agent is selected from the group consisting of
food-grade fatty acids, food-grade oils, food-grade waxes, and
food-grade gums.
25. The pharmaceutical preparation of claim 20, wherein the
hydrophobization agent is a stearic compound and the inorganic
particles are coated with the stearic compound.
26. The pharmaceutical preparation of claim 20, wherein the
hydrophobization agent is magnesium stearate.
27. The pharmaceutical preparation of claim 20, wherein the
hydrophobization agent is food-grade mineral oil.
28. An acetaminophen pharmaceutical preparation comprising: (a)
acetaminophen; and (b) a coated conditioner comprising: (i)
inorganic particles; and (ii) 1 wt % to about 20 wt %, based on the
total weight of the conditioner, of an hydrophobization agent.
29. The acetaminophen pharmaceutical preparation of claim 28,
wherein the preparation in the form of a tablet.
Description
BACKGROUND OF THE INVENTION
[0001] For the last several years materials such as silica, sodium
aluminosilicates, kaolin clays, tricalcium phosphate, and calcium
silicates have been used as "conditioners" in dry and powdered
foods to prevent caking and encourage the free flow of powdered
food particles. In pharmaceuticals, fumed silica has been widely
used as an excipient (conditioner or glidant) for the same reasons.
These conditioners absorb moisture from the atmosphere or package
to prevent the food particles from sticking together in moisture or
pressure cakes and also act as "ball bearings" to coat the surface
of the food particles, thus preventing agglomeration among adjacent
particles. These conditioners, also known as free flow, and
anticaking agents are permitted for use at levels less than or
equal to 2.0 wt % in the final food product by the U.S. Food and
Drug Administration. Additionally these conditioners may also be
used in other applications such as fertilizers, pesticides, and
polymers.
[0002] While these conditioners are used in many
commercially-prepared food powders susceptible to pressure or
moisture caking, they lack efficacy for use in many
pharmaceuticals, as well as certain food products that are
hygroscopic, contain high concentrations of proteinaceous material,
or have a high content of fats and oils such as garlic powder,
de-lactosed milk powder or hydrolyzed vegetable powder. In fact,
for many foods and pharmaceuticals a suitable conditioner is not
available. Certain materials, such as the J. M. Huber Corporation's
Zeosyl.RTM. T 166 (a silica treated with a siloxane to render the
silica hydrophobic) can significantly inhibit caking in foods and
pharmaceuticals. However, silane-treated silicas are only permitted
in food applications as defoaming agents for beet and cane sugar.
They are not permitted for use as food conditioners.
[0003] Thus for many pharmaceuticals and food products there is no
approved commercially-available conditioner that provides excellent
anti-caking performance. For example, the common pain reliever
acetaminophen (N-acetyl-para-aminophenol) has a tightly packed
crystalline form that often results in the formation of pressure
and moisture cakes of the powder during storage, leading to poor
flow performance. Commercially-available fumed silicas, such as
Cab-O-Sil.RTM. M5 from the Cabot Corporation, Bellrica, Mass.,
provide some improvement in flow performance, but they do not
completely address the problem.
[0004] Given the forgoing there is a continuing need for chemical
conditioners suitable for use in certain pharmaceuticals and food
products that provide excellent anti-caking properties to ensure
good flow performance, while at the same time present no health or
safety concerns that would prohibit their use by food safety
regulatory authorities.
BRIEF SUMMARY OF THE INVENTION
[0005] The invention includes an edible composition comprising a
coated conditioner, the conditioner containing a hydrophobization
agent and inorganic particles
[0006] The invention also includes a pharmaceutical preparation
comprising a pharmaceutically active ingredient and a coated
conditioner, the conditioner containing inorganic particles and a
hydrophobization agent.
[0007] The invention also includes an acetaminophen pharmaceutical
preparation comprising acetaminophen, and a coated conditioner
comprising (i) inorganic particles; and (ii) 1 wt % to about 20 wt
%, based on the total weight of the conditioner, of an
hydrophobization agent.
DETAILED DESCRIPTION OF THE INVENTION
[0008] All parts, percentages and ratios used herein are expressed
by weight unless otherwise specified. All documents cited herein
are incorporated by reference.
[0009] By "mixture" it is meant any combination of two or more
substances, in the form of, for example without intending to be
limiting, a heterogeneous mixture, a suspension, a solution, a sol,
a gel, a dispersion, or an emulsion.
[0010] By "coated" it is meant that the specified coating
ingredient covers at least a portion of the outer surface of a
particle or substrate.
[0011] By "inorganic particulates" it is meant both naturally
occurring inorganic minerals and synthetically produced inorganic
compounds.
[0012] By "food product" it is meant any product meant to be
consumed, as well as additives to food products such as, without
intending to be limiting, spices, seasonings, food colorants,
anti-caking and free flow agents.
[0013] The present invention relates to coated conditioners that
when incorporated into powdered pharmaceutical or food products
inhibit caking and promote the free flow of the powder. These
coated conditioners are a mixture of a hydrophobization agent (such
as a stearic compound or an oil) and well-known inorganic
particulates such as kaolin clay, silica, silicates, phosphates,
and calcium carbonates. These coated conditioners are not only
functionally effective, but because the conditioners are merely a
mixture of two components (bydrophobization agent and inorganic
particulates) that have previously been approved food additives,
then the conditioners are safe for use in pharmaceuticals and food
products.
[0014] The ingredients of the coated conditioner as well as a
method for making the coated conditioner will now be discussed in
detail. Then powdered pharmaceutical or food products that make use
of the coated conditioners will be discussed and examples of such
products provided.
[0015] The coated conditioners prepared according to the present
invention are composed of at least two components: inorganic
particles and hydrophobizing compounds. The inorganic particles are
selected from any inorganic compounds commonly used as conditioners
in food and pharmaceutical powders, such as silica (such as
precipitated silica or fumed silica and silica gel), precipitated
or ground calcium carbonates, kaolin clays, silicates (such as
calcium silicate, magnesium silicate, aluminum calcium silicate,
tricalcium silicate, sodium calcium aluminosilicate, sodium
magnesium aluminosilicate, and sodium aluminosilicate) and
phosphates (such as tricalcium phosphate, dicalcium phosphate,
monocalcium phosphate, magnesium phosphate). Preferably, the
inorganic particles serve as substrates, i.e., the inorganic
particles are coated with the hydrophobization agent.
[0016] The preferred silicas are amorphous precipitated silicas
that are produced from a liquid phase by acidulating an alkali
metal silicate with a strong acid such as sulfuric acid, in the
presence of heat. Useful techniques for conducting the
precipitation (acidulation) reaction itself to produce homogenous
amorphous silica particles are widely known and understood. The
resulting silica precipitate is filtered, washed, and dried in
manners such as customarily practiced. Examples of the many
patented publications describing such precipitated silicas include
U.S. Pat. Nos. 4,122,161, 5,279,815 and 5,676,932 to Wason et al.,
and U.S. Pat. Nos. 5,869,028 and 5,981,421 to McGill et al.
[0017] After being produced by the aforementioned liquid phase
method, the precipitated silica may then be milled to obtain the
desired particle size of between about 4 .mu.m to 25 .mu.m, such as
about 4 .mu.m to about 15 .mu.m. Said silicas will preferably have
oil absorption of about 50 ml/100 g to about 475 ml/100 g. Suitable
silicas are manufactured by the J.M. Huber Corporation, Edison,
N.J., and are sold in different grades under the trademarks
Zeofree.RTM., Zeosyl.RTM. and Zeothix.RTM..
[0018] Synthetic amorphous alkaline earth metal silicates, such as
amorphous calcium silicate, may also be used as the inorganic
particles. These silicates are most typically prepared by the
reaction of a reactive silica with an alkaline earth metal
reactant, preferably an alkaline earth metal oxide or hydroxide,
and a source of aluminum such as sodium aluminate or alumina.
Because the final properties of the silicate are dependent on the
reactivity of the silica, the silica source is preferred to be a
clay which has been treated with a mineral acid (such as sulfuric
acid) to produce alum (aluminum sulfate) and an insoluble reactive
silica. A suitable example of this is sulfuric acid leached
reactive clay. Suitable synthetic amorphous alkaline earth metal
silicates are manufactured by the J.M. Huber Corporation and are
sold in different grades under the trademark Hubersorb.RTM. Methods
and techniques for preparing these silicas are discussed in greater
detail in U.S. Pat. No. 4,557,916. Other suitable silicates are
available from J.M. Huber Corporation such as sodium
aluminosilicate sold under the trademark Zeolex.RTM. and sodium
magnesium aluminosilicate sold under the trademark Hydrex.RTM..
[0019] Also suitable for use as inorganic particles are ground
calcium carbonate or precipitated calcium carbonate. Ground calcium
carbonate is first mined and then ground to the appropriate
particle size. Optionally, ground calcium carbonate may be
classified into more narrow particle size fractions. Precipitated
calcium carbonate is typically obtained by exposing calcium
hydroxide slurry (i.e., milk of lime) to a carbonation reaction.
This may be done by injecting carbon dioxide gas into a reaction
vessel containing aqueous calcium hydroxide slurry. Methods and
techniques for preparing these precipitated calcium carbonates are
discussed in greater detail in U.S. Pat. No. 4,888,160. Suitable
precipitated calcium carbonates are manufactured by the J.M. Huber
Corporation and are sold in different grades under the trademark
HuberCal.RTM..
[0020] Also suitable for use as inorganic particles are clays such
as kaolin clays. These clays are produced by first mining raw clay,
and then subjecting the mined clay to several beneficiating steps
until it is suitable for use in a consumer product. The
beneficiating steps include, for example: removing grit particles,
sorting the clay particles to obtain a more desirable particle size
distribution; removing several different impurities found in the
raw clay, and steps to impart to the clay a more desirable final
color. Suitable kaolin clays are manufactured by the J.M. Huber
Corporation and are sold in different grades under the trademark
Polygloss.RTM..
[0021] Hydrophobization agents include food-grade fatty acids,
particularly stearic compounds, food-grade oils, and food-grade
waxes and gums. Suitable fatty acids include capric, capryllic,
lauric, myristic, oleic, palmitic and stearic acids, as well as the
fatty acid compounds listed in Title 21 C.F.R. (the United States'
Code of Federal Regulations) as permitted for direct addition to
food, feed or pharmaceuticals. Suitable stearic compounds include
stearic acids, salts of stearic acid and esters of stearic acid.
Suitable salts of stearic acid include magnesium stearate, calcium
stearate, potassium stearate and zinc stearate. A suitable
magnesium stearate is the vegetable-based, food grade magnesium
stearate available from Ferro Chemicals, Cleveland, Ohio under the
Synpro.RTM. trademark. Suitable esters of stearic acid include
alcohol stearic acid esters such as glycerylmonostearate and
triglyceryl stearate. Suitable esters of stearic acid include
alcohol stearic acid esters such as glyceryl monostearate and
glyceryl tristearate, as well as other esters such as glyceryl
palmitostearate, and sorbitan monostearate. Glyceryl monostearate
and glyceryl tristearate are available from Patco Corporation,
Wilmington, Del. under the trademarks Pationic.RTM. 901 and
Pationic.RTM. 919, respectively.
[0022] Food-grade oils are those oils listed in 21 C.F.R. as
permitted for direct addition to food, feed or pharmaceuticals.
Suitable food-grade oils include white mineral oil, rapeseed oil,
soybean oil, castor oil, coconut oil and oils defined as "essential
oils" by the F.D.A. in 21 C.F.R. .sctn.182.20. Suitable food-grade
waxes and gums may also be located in 21 C.F.R. Suitable food-grade
waxes include candelilla, carnuba and paraffin waxes. Suitable
food-grade gums include karaya gum, gum tragacanth, carrageenan
gum, xanthan gum, and guar gum.
[0023] A preferred process for combining the aforementioned
ingredients to form a coated conditioner (in which the
hydrophobization agents are stearic compounds) can be summarized as
follows. In a first step of this process, an amount of the
inorganic particles is added to a mixing bowl and preferably heated
to a temperature of 10.degree. F. to 30.degree. F. above the
melting point of the stearic compound. The rotating blades of the
mixer are turned on, a stearic compound added to the bowl. Mixing
continues for about 30 minutes. After mixing is completed, the
material inside the mixing bowl (the coated conditioner) is allowed
to cool before it is added to a powdered food or pharmaceutical
product. When the hydrophobization agent is an oil, an identical
process as that described is followed with the exception that no
heating is required, because the oils are liquid at ambient
temperature.
[0024] The invention will now be described in more detail with
respect to the following, specific, non-limiting examples.
EXAMPLES
[0025] In Examples 1-8, coated conditioners that are a mixture of a
stearic compound and inorganic particles were prepared according to
the present invention. The inorganic particles have median particle
size and oil absorption values given in Table A, below (methods for
determining particle size and oil absorption value are discussed
below).
[0026] In this process, first, an amount of inorganic particles,
such as silica, calcium carbonate or kaolin clay (as indicated in
Table I below) was added to a mixing bowl and the mixing bowl
attached to a Kitchen Aid Heavy Duty mixer, model K5SS. To control
the temperature of the mixing bowl contents, a thermal jacket was
wrapped around it so as to heat the mixing bowl to increase the
temperature of the mixing bowl contents. The temperature of its
contents were measured by a thermocouple placed in contact with the
mixing bowl contents, and the temperature was electronically
regulated through a solid state temperature controller connected to
both the thermocouple and the thermal jacket.
[0027] The temperature controller was set at 177.degree. C. and the
mixer turned on low. After the temperature of the inorganic
particles in the mixing bowl reached 177.degree. C., powdered
magnesium stearate (vegetable-based, food grade magnesium stearate
available from Ferro Chemicals, Cleveland, Ohio under the
Synpro.RTM. trademark) was added to the inorganic particles in the
mixing bowl in the weight proportions set forth in Table 1 below
and mixing was allowed to continue for 10 minutes. The wt % of
magnesium stearate added is based on the total weight of the coated
conditioner (i.e., the weight of the inorganic substrate plus the
weight of magnesium stearate). Following mixing the resulting
coated conditioner powder was allowed to cool to ambient
temperature. During mixing, the magnesium stearate was melted onto
the particulate inorganic substrate so that the coated conditioner
was a mixture of magnesium stearate and the particulate mineral
substrate.
[0028] The particle size and the oil absorption of the inorganic
particles used in the following examples are as follows:
1TABLE A Median Particle Size Oil Absorption Inorganic Particle
.mu.m mL/100 g Zeofree 80 silica 14 195 Zeothix 265 silica 4 220
HuberCal 250 GCC 14 13 Hubersorb 600 calcium silicate 6 475
Polygloss 90 clay 0.4 42
[0029] Zeofree.RTM. 80 and Zeothix.RTM. 265 amorphous precipitated
silicas are available from the J.M. Huber Corporation.
Polygloss.RTM. 90, a kaolin clay, and HuberCal.TM. 250, a ground
calcium carbonate, are both available from the J.M. Huber
Corporation. Hubersorb.RTM. 600 is a calcium silicate from the J.M.
Huber Corporation
[0030] The oil absorption was measured using linseed oil by the
rubout method. In this test, oil is mixed with a silica and rubbed
with a spatula on a smooth surface until a stiff putty-like paste
is formed. By measuring the quantity of oil required to have a
paste mixture, which will curl when spread out, one can calculate
the oil absorption value of the silica--the value which represents
the volume of oil required per unit weight of silica to completely
saturate the silica sorptive capacity. Calculation of the oil
absorption value was done according to equation (I): 1 Oil
absorption = ml oil absorbed weight of silica , grams .times. 100 =
ml oil / 100 gram silica ( I )
[0031] The particle size was determined using a Model LA-910 laser
light scattering instrument available from Horiba Instruments,
Boothwyn, Pa. A laser beam is projected through a transparent cell
which contains a stream of moving particles suspended in a liquid.
Light rays which strike the particles are scattered through angles
which are inversely proportional to their sizes. The photodetector
array measures the quantity of light at several predetermined
angles. Electrical signals proportional to the measured light flux
values are then processed by a microcomputer system to form a
multi-channel histogram of the particle size distribution.
[0032] The compositions of the coated conditioners of example
numbers 1-8 are as follows:
2TABLE I Inorganic Wt % of Magnesium Example No Substrate Stearate
1 Zeofree 80 2 2 Zeofree 80 4 3 Zeothix 265 2 4 Zeothix 265 4 5
Polygloss 90 2 6 Polygloss 90 4 7 HuberCal 250 2 8 HuberCal 250
4
[0033] Further coated conditioner samples (Examples 9-25) were
prepared in a manner similar to that set forth above for examples
1-8, except that a Thysson Henschel FM 100 mixer was used. The
participation inorganic substrates, as indicated in Table II below,
were placed in a mixing bowl attached to the mixer and preheated to
77.degree. C. while the mixing blade rotated at 860 rpm. After
reaching 77.degree. C., an amount of stearate, as indicated in
table II below, is added. The inorganic particles and the stearate
are allowed to mix at 77.degree. C. for 10 minutes. The exception
is that when magnesium stearate is used, the temperature is set to
170.degree. C. Following mixing the resulting coated conditioner
powder is allowed to cool to ambient temperature.
[0034] The compositions of the coated conditioners of example
numbers 9-25 are as follows:
3TABLE II Example Inorganic Weight % of No Substrate Stearate
Glyceryl stearate 9 Zeofree 80 Glyceryl monostearate 2 10 Zeofree
80 Glyceryl monostearate 4 11 Zeofree 80 Glyceryl tristearate 2 12
Zeofree 80 Glycery tristearate 4 13 Zeothix 265 Glyceryl
monostearate 2 14 Zeothix 265 Glyceryl monostearate 4 15 Zeothix
265 Glyceryl tristearate 2 16 Zeothix 265 Glyceryl tristearate 4 17
Polygloss 90 Glyceryl monostearate 2 18 Polygloss 90 Glyceryl
monostearate 4 19 Polygloss 90 Glyceryl tristearate 2 20 Polygloss
90 Glyceryl tristearate 4 21 HuberCal 250 Glyceryl monostearate 2
22 HuberCal 250 Glyceryl monostearate 4 23 HuberCal 250 Glyceryl
tristearate 2 24 HuberCal 250 Glyceryl tristearate 4 25 Hubersorb
600 Magnesium Stearate 4
[0035] Hubersorb 600 calcium silicate is available from the J.M.
Huber Corporation. The wt % of the stearate added is based on the
total weight of the coated conditioner (weight of mineral substrate
plus weight of the stearate).
[0036] In Examples 26-29, coated conditioners that are a mixture of
mineral oil and precipitated silica were prepared according to the
present invention. First, 100 grams of precipitated silica (as
indicated in Table III, below) was added to a mixing bowl and the
mixing bowl attached to a laboratory-scale Hobart mixer. The mixer
was turned on low speed and at ambient temperature 4.0% or 10.0% of
mineral oil was added and allowed to mix with the silica for 10
minutes (as indicated in Table III, below).
4TABLE III Inorganic Mineral Oil Example Number Substrate Addition
26 Zeofree 80 4% 27 Zeofree 80 10% 28 Zeothix 265 4% 29 Zeothix 265
10%
[0037] The likelihood of a powder to form a moisture cake was
evaluated using the moisture caking test. Before actual testing of
the conditioned powder in the moisture cake itself (i.e.,
pharmaceutical or food powder containing a conditioner) was done, a
baseline correlation between moisture and caking for unconditioned
pharmaceutical or food powder was determined. To established this
correlation, acetaminophen powder is titrated with a minimum amount
of water to produce near 0% caking, and also an acetaminophen
powder is titrated with a maximum amount of water to produce 70-80%
caking. These points are then plotted along a straight line, and
the amount of water needed to produce about 50% caking is the
amount then used for the remaining conditioned acetaminophen powder
samples to be tested.
[0038] The above moisture measurements were carried out as follows.
A sufficient amount of screened, unconditioned sample was placed
into an 8 oz. Spex.RTM. Mill jar so that the jar was about one-half
full. Either 1 ml or 1 g of water was titrated or weighed onto the
sample in the jar, and then the jar and its contents were placed on
the Spex Mill (model 8000-115 available from Spex Corporation,
Edison, N.J.) for 30 seconds. Then a small aluminum pan was
prepared for use by pressing the lid of the Spex Jar to the bottom
of the pan to mold the contour of the pan to the shape of the lid.
20 g of wet sample was then weighed onto the pan. Then from this 20
g of sample a level cake was formed by placing a jar filled with
lead shot, lid side down, on each sample. Samples were then placed
in an oven for at least 15 minutes at 50.degree. C. to expel the
added moisture and set the cake. Sample weight should be checked to
confirm that all of the added water has been driven off. Longer
times or higher temperatures may be required to remove all of the
water. As the testing is done in triplicate, three jars are
prepared for each sample component.
[0039] the samples were then removed from the oven and allowed to
cool for ten minutes to room temperature. If the samples are not
allowed to cool to room temperature, artificially low % moisture
caking will result. The samples were not allowed to cool more than
15 minutes (because once they are cooled, samples can begin to
absorb moisture, which can soften the cake and result in an
artificially low % moisture cake).
[0040] Next, a #12 Tyler screen was inverted and centered over each
aluminum pan, and the aluminum pan held against the # 12 screen, at
the same time that the sample was carefully inverted over the
screen so that the cake comes to rest on the #12 screen as the
aluminum pan is removed. The screen was then transferred to a
Thomas orbital sieve shaker (available from Thomas Scientific
Apparatus) without breakage, and the caked sample vibrated on the
Thomas Shaker for one minute. The amount of sample remaining on the
screen is weighed, and percent cake is calculated as in equation
(II): 2 grams of cake left on screen ( x - xy z + y ) * 100 = %
cake ( II )
[0041] wherein:
[0042] x=g of sample used in aluminum pan
[0043] y=ml H.sub.2O added to sample in jar
[0044] z=g of sample added to jar
[0045] After the percent cake has been determined in triplicate for
1 ml of added water, then the process described above was repeated
using 2 ml of water, then 3 ml, etc., until 80% caking is reached.
Products, which are very sensitive to moisture may require
increments of water below 1 ml. Water addition levels should be
adjusted until there are at least four data points on the caking
curve between 10-80%. The results of the % cake test for garlic
powder and acetaminophen are set forth below.
[0046] To measure the loose bulk density, a modified 250-mL
graduated cylinder is utilized. The cylinder has been modified such
that the cylinder top is level with the 1100 ml mark, by cutting
off the cylinder at the 100-mL mark. The empty cylinder weight is
recorded as the "tare weight". The sample powder was poured into
the modified cylinder until overflowing. The level of powder in the
cylinder was immediately leveled-off by scraping across the top
with a spatula; this leveling-off step was done as quickly as
possible to prevent settling of the powder, which would give
artificially high loose bulk density values. Any additional excess
powder along the sides or base of the graduated cylinder was also
brushed off and the cylinder weighed, with the weight recorded as
the "total weight". Any volume change noticed after the powder has
been leveled off and excess powder brushed away is to be ignored,
because this volume change is due to the tendency of the powder to
pack down. The loose bulk density is calculated from equation II: 3
Loose Bulk Density , g / ml = total wt . - tare wt . 100 ( II )
[0047] Another useful measure of powder flowability is the
avalanche time, which is measured as the "Aeroflow parameter". The
shorter the time between avalanches, the more free flowing the
powder. In this test, first an amount of unconditioned sample was
used to determine the weight needed to fill a 100 ml graduated
cylinder, as in the loose bulk density test, above. This weight was
then used for all runs of the Aeroflow.RTM. tests. An Aeroflow.RTM.
Powder Flowability Analyzer Model 0-8030 from TSI Incorporated of
St. Paul, Minn. was used in these tests. In the first step of these
tests, a ring of masking tape was applied to the inner surface of
an Aeroflow testing drum. The masking tape acts, in effect, as a
gasket to prevent the powder from leaking during operation. The
powder sample was then loaded into the drum and the drum placed
into the Aeroflow testing device. Using the computer interface, the
Aeroflow test was selected, and the Hardware Configuration settings
on the instrument checked to verify that the drum speed is 60 rpm.
The "apply" feature was then selected and the drum allowed to
rotate for 5 minutes. After 5 minutes the device was manually
stopped by the operator by depressing the "Close" button. Then the
mean avalanche time was determined with the drum speed set at 60
rpm and the test duration set at 300 seconds. For each sample, the
test was repeated one additional time and the results averaged and
expressed in seconds.
[0048] Also measured was the Flowdex parameter. Flowdex is a
measure of flowability that simulates the flowability of a powder
in a silo. 25 g of a sample is placed in a funnel, which is placed
above the Flowdex straight walled, open cylinder. In the bottom of
the cylinder is a plate with an opening of known diameter. Several
different plates with different diameter openings ("orifices") are
available, so the plates can be interchanged until the minimum
opening required for the sample to flow through is determined. The
smaller the opening required for a given material to flow through,
the more easily the material will flow in a bag house or silo.
[0049] In the test, the Flowdex apparatus (model 21-100-004
available from Hanson Research, Chatsworth, Calif.) is prepared in
accordance with the manufacturer's instructions with the smallest
orifice supplied by the manufacturer installed (and a removable
stopper installed under the orifice). 25.00 g of the sample is
weighed and poured into the upper funnel, and the timer started.
After 30 seconds, the stopper is removed from the orifice, and the
sample allowed to flow (if possible) though the orifice. The device
is inspected to determine if the sample flowed through the orifice
such that the bottom of the instrument is visible, if the bottom of
the instrument is visible, the orifice diameter is recorded, and
this is taken as the Flowdex value. If the bottom is not visible,
the orifice is replaced with the next larger size and the above
procedure repeated. Once an orifice has been found that permits
flow, the test is repeated with the same orifice to confirm the
orifice diameter value.
[0050] To demonstrate their efficacy in consumer products, coated
conditioners prepared according to Examples 1-24 were incorporated
into acetaminophen powder compositions at three different
concentration levels, 0.1 wt %, 0.5 wt %, 1.0 wt %. As a control
the most widely used conditioner for acetaminophen, Cab-O-Sil.RTM.
M5 fumed silica, was added to a separate acetaminophen composition.
As discussed above, acetaminophen has a tightly packed crystalline
form that often results in the formation of pressure and moisture
cakes of the powder during storage.
[0051] The percent cake, loose bulk density, the Aeroflow parameter
and the Flowdex parameter were measured for acetaminophen and the
Results are set forth in tables IV-VII, below:
5TABLE IV Moisture Caking of Acetaminophen Concentration of Coated
Conditioner (in Wt %) Conditioner 0.1 0.5 1.0 Unconditioned 46.0
46.0 46.0 Control Conditioner: 61.8 85.7 85.0 (Cab-O-Sil .RTM. M5)
Example 1 50.9 75.8 80.8 Example 2 58.1 78.7 79.6 Example 3 52.1
83.4 -- Example 4 -- 81.9 85.4 Example 5 45.0 63.4 85.9 Example 7
47.8 46.0 52.0 Example 8 44.2 48.6 49.5 Example 9 52.1 79.1 84.7
Example 10 62.2 71.0 52.0 Example 11 71.2 65.2 79.0 Example 12 55.4
83.0 67.4 Example 13 65.8 12.4 80.3 Example 14 63.2 81.9 69.4
Example 15 65.8 64.7 80.3 Example 16 46.1 -- 68.9 Example 17 50.8
13.6 91.1 Example 18 52.1 78.2 89.5 Example 19 50.4 53.9 72.8
Example 20 47.6 54.8 74.4 Example 21 49.4 42.4 42.2 Example 22 40.8
34.9 38.5 Example 23 47.3 46.3 43.2 Example 24 45.8 42.8 47.5
[0052] Moisture caking is not a significant problem for
unconditioned acetaminophen powder. However, it is important that
conditioner added to acetaminophen to improve flow not be
deleterious to moisture caking. It is seen from the above data that
the industry standard used to improve flow of acetaminophen
(Cab-O-Sil M5) actually is detrimental to moisture caking, while
most of the inventive example conditioners perform better than
Cab-O-Sil M5 and some actually improve moisture caking. Tables V
and VI below show the flow properties of these same
conditioners.
6TABLE V Aeroflow Parameter of Acetaminophen Concentration of
Coated Conditioner (in Wt %) Conditioner: 0.1 0.5 1.0 Unconditioned
3.00 3.00 3.00 Control Conditioner: 1.86 1.88 2.02 (Cab-O-Sil M5)
Example 1 1.67 1.70 1.91 Example 2 1.82 1.79 1.86 Example 3 1.72
1.83 1.89 Example 4 1.81 1.81 1.92 Example 5 -- 2.25 2.13 Example 6
2.09 2.27 2.15 Example 7 2.77 2.74 3.05 Example 8 3.06 2.98 2.77
Example 9 1.85 1.74 1.99 Example 10 1.78 1.72 1.94 Example 11 1.84
-- 1.96 Example 12 1.80 1.78 1.97 Example 13 1.75 1.85 1.97 Example
14 1.73 1.85 1.87 Example 15 1.77 1.78 2.06 Example 16 1.84 1.94
2.06 Example 17 2.68 2.49 2.02 Example 18 2.17 2.30 2.20 Example 19
2.10 2.27 2.00 Example 20 2.33 2.25 2.02 Example 21 2.77 2.80 2.85
Example 22 3.31 3.24 3.11 Example 23 2.72 2.70 2.87 Example 24 3.08
2.85 2.91
[0053] As can be seen from the data in Table V, the acetaminophen
powder incorporating coated conditioners prepared according to
examples 1, 2, 3, 4, 9, 10, 11, 12, 13, and 14 had an improved
measured Aeroflow Parameter (i.e., shorter avalanche times) when
compared to acetaminophen powder incorporating the control fumed
silica conditioner.
7TABLE VI Flowdex Parameter of Acetaminophen Concentration of
Conditioner (in Wt %) Coated conditioner: 0.1 0.5 1.0 Unconditioned
22 22 22 Control Conditioner: 4 5 7 (Cab-O-Sil M5) Example 1 4 4 8
Example 2 4 5 7 Example 3 4 7 6 Example 4 4 5 10 Example 5 7 7 8
Example 6 6 4 7 Example 7 14 18 16 Example 8 22 20 22 Example 9 4 5
7 Example 10 4 4 6 Example 11 5 -- 8 Example 12 4 5 7 Example 13 4
4 7 Example 14 4 5 5 Example 15 4 7 8 Example 16 5 9 14 Example 17
14 4 4 Example 18 10 5 6 Example 19 14 6 8 Example 20 10 8 9
Example 21 16 18 18 Example 22 22 20 22 Example 23 14 22 22 Example
24 18 20 20
[0054] As can be seen in Table VI, all of the acetaminophen powders
incorporating a coated conditioner prepared according to the
present invention and using a silica as the inorganic particulate
showed improved performance on the Flowdex test (i.e., passed
through a narrower orifice) when compared to untreated
acetaminophen powders. Many of the acetaminophen powders
incorporating a coated conditioner prepared according to the
present invention also showed improved performance on the Flowdex
test when compared to acetaminophen powders incorporating the
Cab-O-Sil product.
8TABLE VII Loose Bulk Density of Acetaminophen Concentration of
Conditioner (in Wt %) Coated conditioner: 0.1 0.5 1.0 Unconditioned
0.656 0.656 0.656 Control Conditioner: 0.699 0.674 0.645 (Cab-O-Sil
M5) Example 1 0.707 0.700 0.678 Example 2 0.711 0.700 0.693 Example
3 0.703 0.693 0.689 Example 4 0.711 0.701 0.667 Example 5 0.700
0.696 0.695 Example 6 0.695 0.698 0.700 Example 7 0.684 0.680 0.681
Example 8 0.661 0.665 0.665 Example 9 0.715 0.705 0.696 Example 10
0.719 0.706 0.698 Example 11 0.714 0.704 Example 12 0.727 0.714
0.699 Example 13 0.742 0.728 0.702 Example 14 0.733 0.712 0.699
Example 15 0.711 0.693 0.662 Example 16 0.724 0.708 0.673 Example
17 0.690 0.699 0.686 Example 18 0.708 0.711 0.697 Example 19 0.705
0.710 0.689 Example 20 0.717 0.710 0.700 Example 21 0.660 0.667
0.662 Example 22 0.659 0.654 0.651 Example 23 0.665 0.668 0.681
Example 24 0.655 0.650 0.659
[0055] Loose bulk density measurements generally show whether a
material has been conditioned properly. A material that has been
conditioned properly (i.e., that has maximum flow and minimum
caking) will typically have an increased bulk density. Increased
loose bulk density means that the product container package will
not have to be enlarged when a conditioner is used. As can be seen
in Table VII, several of the acetaminophen powders incorporating a
coated conditioner prepared according to the present invention
showed increased loose bulk density at all concentration levels
when compared to the Cab-O-Sil product.
[0056] To demonstrate their efficacy in food products, coated
conditioners prepared according to Examples 1-24 were incorporated
into garlic powder compositions at three different concentration
levels: 0.5 wt %, 1.0 wt %, 2.0 wt %. As a control, a widely used
conditioner for food products, J.M. Huber's Zeofree 80, was also
added to the garlic powder compositions.
9TABLE VIII % Moisture Caking in Garlic Powder Concentration of
Coated Conditioner (in Wt %) Conditioner: 0.5 1.5 2.00
Unconditioned Garlic 65.91 65.91 65.91 Powder Example 1 60.31 24
14.1 Example 2 56.62 21.01 13.5 Example 3 44.62 12.31 5.88 Example
9 53.7 34.92 20.7 Example 12 60.73 24.28 20.2 Example 27 62.68
37.98 25.2 Example 29 53.67 23.96 12.5 Control Conditioner: 48.66
19.62 13.7 Zeofree 80
[0057] As is seen in from the data in Table VIII above, all of
these conditioners, prepared in accordance with the invention,
reduce the moisture caking of garlic powder. At the optimum
treatment level of 2%, example 2, 3 and 29 conditioners performed
better than the control conditioner.
10TABLE IX Aeroflow of Garlic Powder Concentration of Coated
Conditioner (in Wt %) Conditioner: 0.5 1.5 2.00 Unconditioned
Garlic 2.93 2.93 2.93 Powder Example 1 2.36 2.41 2.55 Example 2
2.39 2.38 2.38 Example 3 2.59 2.62 2.44 Example 9 2.49 2.55 2.37
Example 12 2.41 2.38 2.44 Example 27 2.19 2.04 2.21 Example 29 2.26
2.17 2.02 Control Conditioner: 2.56 2.58 2.52 Zeofree 80
[0058] As can be seen from the data in Table IX, the garlic powder
incorporating coated conditioners prepared according to examples
1-3, 9, 12, 27, and 29 had an improved measured Aeroflow Parameter
(i.e., shorter avalanche times) when compared to the garlic powder
incorporating the control coated conditioner, Zeofree 80. Shorter
avalanche times were not obtained with the coated conditioners
prepared according to the other examples and so the results are not
shown.
11TABLE X Flowdex of Garlic Powder Concentration of Coated
Conditioner (in Wt %) Conditioner: 0.5 1.5 2.00 Unconditioned
Garlic 26 26 26 Powder Example 1 28 28 28 Example 2 24 26 24
Example 3 28 28 30 Example 9 24 24 26 Example 12 26 26 26 Example
27 28 26 24 Example 29 26 26 26 Control Conditioner: 26 28 30
Zeofree 80
[0059] As can be seen in Table X, the garlic powders incorporating
a coated conditioner prepared according to examples 2-3, 9, 12, 27,
and 29 showed improved performance on the Flowdex test when
compared to the garlic powder incorporating the control
conditioner, Zeofree 80.
12TABLE XI Loose Bulk Density of Garlic Powder Concentration of
Coated Conditioner (in Wt %) Conditioner: 0.5 1.5 2.00
Unconditioned Garlic 0.496 0.496 0.496 Powder Example 29 0.497
0.469 0.459 Example 27 0.512 0.486 0.467 Example 1 0.495 0.475
0.453 Example 2 0.509 0.474 0.457 Example 9 0.512 0.465 0.461
Example 12 0.488 0.491 0.466 Example 3 0.482 0.449 0.471 Zeofree 80
0.513 0.479 0.47
[0060] The loose bulk density of garlic powder treated with
conditioners 2, 9, and 27 at loading levels of 0.5% increased
(improved). All of the conditioners decreased the garlic powder
loose bulk density at higher loading levels.
[0061] It will be appreciated by those skilled in the art that
changes could be made to the embodiments described above without
departing from the broad inventive concept thereof. It is
understood, therefore, that this invention is not limited to the
particular embodiments disclosed, but it is intended to cover
modifications within the spirit and scope of the present invention
as defined by the appended claims.
* * * * *